The elucidation of molecular mechanism of extracorporeal shock wave therapy for skin ulcer in systemic sclerosis

• Project/Area Number: 18K08401
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Tohoku University
• Principal Investigator: Fujii Hiroshi 東北大学, 大学病院, 准教授 (30531321)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 強皮症 / 体外衝撃波 / 皮膚潰瘍 / FOSB / 体外衝撃波照射 / FosB / 血管新生 / 難治性皮膚潰瘍

Outline of Final Research Achievements

Gene expression profiling analysis of human dermal microvascular endothelial cells (HDMEC) with microarray revealed that the transcriptional factor FOSB was more than 10-folds increased after irradiation of shock wave. Shock wave treatment induced the gene expression of FOSB and CXCL2 in rat skin. Up-regulator analysis showed that the gene set induced by shock wave treatment highly correlated with PMA-induced genes. The aberrant expression of FOSB in HDMEC revealed that both of VEGF and CXCL2 were increased co-cultured with PMA, whereas none of these genes were changed without PMA.

Academic Significance and Societal Importance of the Research Achievements

全身性強皮症に合併する指尖潰瘍に対する種々の薬剤の治療効果は限定的であり、新たな発想に基づく新規治療法の開発を要する。本研究で皮膚細胞、皮膚組織への体外衝撃波照射により、転写因子FOSBの誘導が引き起こされ、その後、血管新生ケモカインであるCXCL2の誘導が起こることが示された。このFOSB-CXCL2-血管新生の機序が、創傷治癒に寄与している可能性がある。体外衝撃波照後の早期の遺伝子変化を示したのは、本研究が初めてである。PDE4阻害剤などFOSBの発現を促進する可能性のある薬剤を併用することにより強皮症における体外衝撃波療法の治癒効果改善効果が期待できる。

Research Products

• [Journal Article] Migratory Aortitis Associated with Granulocyte-colony-stimulating Factor (2020)
  • Author(s): Shirai Tsuyoshi、Komatsu Hiroka、Sato Hiroko、Fujii Hiroshi、Ishii Tomonori、Harigae Hideo
  • Journal Title: Internal Medicine Volume: 59 Issue: 12 Pages: 1559-1563
  • DOI: 10.2169/internalmedicine.4331-19
  • NAID: 130007854988
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2020-06-15
  • Peer Reviewed / Open Access
• [Journal Article] JAK2 mutation?positive polycythaemia vera associated with IgA vasculitis and nephrotic syndrome: a case report (2020)
  • Author(s): Kondo Hinako、Watanabe Ryu、Okazaki Soshi、Kuriyama Kaori、Ochi Tetsuro、Yamada Gen、Sugiura Akira、Chiba Hiromu、Tsukada Akira、Taniuchi Shinji、Igarashi Takehiko、Kudo Masataka、Harigae Hideo、Fujii Hiroshi
  • Journal Title: Modern Rheumatology Case Reports Volume: 4 Issue: 2 Pages: 289-295
  • DOI: 10.1080/24725625.2020.1728061
  • Peer Reviewed
• [Journal Article] High Relapse Rate in Patients with Polymyalgia Rheumatica despite the Combination of Immunosuppressants and Prednisolone: A Single Center Experience of 89 patients (2020)
  • Author(s): Okazaki Soshi、Watanabe Ryu、Kondo Hinako、Kudo Masataka、Harigae Hideo、Fujii Hiroshi
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 251 Issue: 2 Pages: 125-133
  • DOI: 10.1620/tjem.251.125
  • NAID: 130007864039
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed / Open Access
• [Journal Article] Successful Treatment of Pulmonary Arterial Hypertension in Systemic Sclerosis with Anticentriole Antibody. (2020)
  • Author(s): Ishii Y, Fujii H, Sugimura K, Shirai T, Hoshi Y, Fujita Y, Shirota Y, Ishii T, Shimokawa H, Harigae H.
  • Journal Title: Case Rep Rheumatol. Volume: 2020 Pages: 1-7
  • DOI: 10.1155/2020/1926908
  • Peer Reviewed / Open Access
• [Journal Article] Identification of two major autoantigens negatively regulating endothelial activation in Takayasu arteritis. (2020)
  • Author(s): Mutoh T, Shirai T, Ishii T, Shirota Y, Fujishima F, Takahashi F, Kakuta Y, Kanazawa Y, Masamune A, Saiki Y, Harigae H, Fujii H.
  • Journal Title: Nat Commun. Volume: 11(1) Issue: 1 Pages: 1-13
  • DOI: 10.1038/s41467-020-15088-0
  • Peer Reviewed / Open Access
• [Journal Article] Better Retention of Abatacept Is Associated with High Rheumatoid Factor: A Five-Year Follow-Up Study of Patients with Rheumatoid Arthritis (2020)
  • Author(s): Okazaki Soshi、Watanabe Ryu、Harigae Hideo、Fujii Hiroshi
  • Journal Title: The Tohoku Journal of Experimental Medicine Volume: 250 Issue: 3 Pages: 153-159
  • DOI: 10.1620/tjem.250.153
  • NAID: 130007805117
  • ISSN: 0040-8727, 1349-3329
  • Peer Reviewed
• [Journal Article] Comment on: Aortarctia: a rare manifestation of relapsing polychondrits (2020)
  • Author(s): Shirai Tsuyoshi、Murakami Koji、Fujii Hiroshi、Ishii Tomonori、Harigae Hideo
  • Journal Title: Rheumatology Volume: 59 Issue: 7 Pages: 1784-1785
  • DOI: 10.1093/rheumatology/keaa019
  • Peer Reviewed